8.4 Stereochemistry of SN2 Reactions ts point of attachment to carbon. For this reason, the SN2 mechanism is sometimes referred to as a direct displacement process. The SN2 mechanism for the hydrolysis of methyl bromide may be represented by a single elementary step HO: t CH3 Br HO---CH3---Br:-HOCH3 : Br Hydroxide Methyl Transition Methyl Carbon is partially bonded to both the incoming nucleophile and the departing halide at the transition state. Progress is made toward the transition state as the nucleophile begins to share a pair of its electrons with carbon and the halide ion leaves, taking with it the pair of electrons in its bond to carbon PROBLEM 8.3 Is the two-step sequence depicted in the following equations con- sistent with the second-order kinetic behavior observed for the hydrolysis of methyl bromide? CH3+ HO CH3OH The SN2 mechanism is believed to describe most substitutions in which simple pri mary and secondary alkyl halides react with anionic nucleophiles. All the examples cited in Table 8. 1 proceed by the Sn2 mechanism (or a mechanism very much like SN2- remember, mechanisms can never be established with certainty but represent only our best present explanations of experimental observations). We'll examine the SN2 mecha- nism, particularly the structure of the transition state, in more detail in Section 8.5 after first looking at some stereochemical studies carried out by Hughes and Ingold. 8.4 STEREOCHEMISTRY OF SN2 REACTIONS What is the structure of the transition state in an SN2 reaction? In particular, what is the spatial arrangement of the nucleophile in relation to the leaving group as reactants pass through the transition state on their way to products? Two stereochemical possibilities present themselves. In the pathway shown in Fig ure &la, the nucleophile simply assumes the position occupied by the leaving group. It attacks the substrate at the same face from which the leaving group departs. This is called front-side displacement, or substitution with retention of configuration In a second possibility, illustrated in Figure 8.1b, the nucleophile attacks the sub strate from the side opposite the bond to the leaving group. This is called"back-side dis placement, "or substitution with inversion of configuration. Which of these two opposite stereochemical possibilities operates was determined in experiments with optically active alkyl halides. In one such experiment, Hughes and Ingold determined that the reaction of 2-bromooctane with hydroxide ion gave 2-octanol having a configuration opposite that of the starting alkyl halid ample have opposite config. CH3(CH,)5 (CH2)5CH3 NaOH opposite signs of rotation, it →>HO CH halide/alcohol pairs. (See Sec. tion 7.5) (S)-(+)-2-Bromooctane (R)-(-)-2-Octanol Back Forward Main MenuToc Study Guide ToC Student o MHHE Website8.4 Stereochemistry of SN2 Reactions 307 its point of attachment to carbon. For this reason, the SN2 mechanism is sometimes referred to as a direct displacement process. The SN2 mechanism for the hydrolysis of methyl bromide may be represented by a single elementary step: Carbon is partially bonded to both the incoming nucleophile and the departing halide at the transition state. Progress is made toward the transition state as the nucleophile begins to share a pair of its electrons with carbon and the halide ion leaves, taking with it the pair of electrons in its bond to carbon. PROBLEM 8.3 Is the two-step sequence depicted in the following equations con￾sistent with the second-order kinetic behavior observed for the hydrolysis of methyl bromide? The SN2 mechanism is believed to describe most substitutions in which simple pri￾mary and secondary alkyl halides react with anionic nucleophiles. All the examples cited in Table 8.1 proceed by the SN2 mechanism (or a mechanism very much like SN2— remember, mechanisms can never be established with certainty but represent only our best present explanations of experimental observations). We’ll examine the SN2 mecha￾nism, particularly the structure of the transition state, in more detail in Section 8.5 after first looking at some stereochemical studies carried out by Hughes and Ingold. 8.4 STEREOCHEMISTRY OF SN2 REACTIONS What is the structure of the transition state in an SN2 reaction? In particular, what is the spatial arrangement of the nucleophile in relation to the leaving group as reactants pass through the transition state on their way to products? Two stereochemical possibilities present themselves. In the pathway shown in Fig￾ure 8.1a, the nucleophile simply assumes the position occupied by the leaving group. It attacks the substrate at the same face from which the leaving group departs. This is called “front-side displacement,” or substitution with retention of configuration. In a second possibility, illustrated in Figure 8.1b, the nucleophile attacks the sub￾strate from the side opposite the bond to the leaving group. This is called “back-side dis￾placement,” or substitution with inversion of configuration. Which of these two opposite stereochemical possibilities operates was determined in experiments with optically active alkyl halides. In one such experiment, Hughes and Ingold determined that the reaction of 2-bromooctane with hydroxide ion gave 2-octanol having a configuration opposite that of the starting alkyl halide. (S)-()-2-Bromooctane C H H3C CH3(CH2)5 Br (R)-()-2-Octanol H CH3 (CH2)5CH3 HO C NaOH ethanol-water CH3Br CH3 Br slow CH3 HO CH3OH fast Hydroxide ion HO Methyl bromide CH3Br Transition state HO CH3   Br Bromide ion Br Methyl alcohol HOCH3 Although the alkyl halide and alcohol given in this ex￾ample have opposite config￾urations when they have opposite signs of rotation, it cannot be assumed that this will be true for all alkyl halide/alcohol pairs. (See Sec￾tion 7.5) Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website